Annals of neurology
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Annals of neurology · Feb 2011
Cerebral amyloid angiopathy pathology and cognitive domains in older persons.
To examine the relation of cerebral amyloid angiopathy (CAA) to cognitive domains in older community-dwelling persons with and without dementia. ⋯ CAA pathology is very common in older community-dwelling persons and is associated with AD pathology. Moderate-to-very severe CAA, but not mild-to-moderate CAA, is associated with lower performance in specific cognitive domains, most notably perceptual speed, separately from the effect of AD pathology.
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Annals of neurology · Feb 2011
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome mutations increase susceptibility to spreading depression.
Migraine with aura is often the first manifestation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome (CADASIL), a disorder caused by NOTCH3 gene mutations expressed predominantly in vascular smooth muscle. Here, we report that cortical spreading depression (CSD), the electrophysiological substrate of migraine aura, is enhanced in mice expressing a vascular Notch 3 CADASIL mutation (R90C) or a Notch 3 knockout mutation. The phenotype was stronger in Notch 3 knockout mice, implicating both loss of function and neomorphic mutations in its pathogenesis. Our results link vascular smooth muscle Notch 3 mutations to enhanced spreading depression susceptibility, implicating the neurovascular unit in the development of migraine aura.